Ondansetron and related 5-HT3 antagonists

Apomorphine is approved for acute off episodes in patients with advanced stages of PD. The onset of effect is within 10 to 20 minutes and the duration of effect is about 60 minutes. It requires premedication with an antiemetic because it causes nausea and vomiting. Antiemetics that block central dopamine worsen the symptoms of PD, and 5-HT3 antagonists, such as ondansetron, can aggravate PD-related hypotension. Trimethobenzamide (300 mg three times daily) should be... 

A second assay which has been used extensively in the characterization of 5-HT3 receptors is the rabbit isolated heart. Both the sympathetic and parasympathetic inputs to the rabbit heart can be influenced by stimulation of 5-HT3 receptors this preparation is usually performed in the presence of atropine to block parasympathetic effects [12]. Under these conditions, 5-HT and other 5-HT3 receptor agonists exert positive effects on rate and contractile force. Selective 5-HT3 receptor antagonists such as MDL 72222 [6], ICS 205-930 [3] and ondansetron [7] block the agonist effects in a concentration-related manner. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

Ye JH, Ponnudurai R, Schaefer R. Ondansetron a selective 5-HT3 receptor antagonist and its applications in CNS-related disorders. CNS Drag Rev 2001 7 199-213. 

A related group of antagonists that possess an imidazole or related heterocyclic terminal amine include ondansetron (Zofran), alosetron (Lotronex), fabesetron, and ramosetron (Fig. 14.15). Many others have been described (75,76). The SARs of 5-HT3 antagonists have been reviewed in detail elsewhere (75,76,77). 

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